Impairment of the TFIIH-associated CDK-activating kinase selectively affects cell cycle-regulated gene expression in fission yeast Journal Article
| Authors: | Lee, K. M.; Miklos, I.; Du, H.; Watt, S.; Szilagyi, Z.; Saiz, J. E.; Madabhushi, R.; Penkett, C. J.; Sipiczki, M.; Bähler, J.; Fisher, R. P. |
| Article Title: | Impairment of the TFIIH-associated CDK-activating kinase selectively affects cell cycle-regulated gene expression in fission yeast |
| Abstract: | The fission yeast Mcs6-Mcs2-Pmh1 complex, homologous to metazoan Cdk7-cyclin H-Mat1, has dual functions in cell division and transcription: as a partially redundant cyclin-dependent kinase (CDK)-activating kinase (CAK) that phosphorylates the major cell cycle CDK, Cdc2, on Thr-167; and as the RNA polymerase (Pol) II carboxyl-terminal domain (CTD) kinase associated with transcription factor (TF) IIH. We analyzed conditional mutants of mcs6 and pmh1, which activate Cdc2 normally but cannot complete cell division at restrictive temperature and arrest with decreased CTD phosphorylation. Transcriptional profiling by microarray hybridization revealed only modest effects on global gene expression: a one-third reduction in a severe mcs6 mutant after prolonged incubation at 36°C. In contrast, a small subset of transcripts (∼5%) decreased by more than twofold after Mcs6 complex function was compromised. The signature of repressed genes overlapped significantly with those of cell separation mutants sep10 and sep15. Sep10, a component of the Pol II Mediator complex, becomes essential in mcs6 or pmh1 mutant backgrounds. Moreover, transcripts dependent on the forkhead transcription factor Sep1, which are expressed coordinately during mitosis, were repressed in Mcs6 complex mutants, and Mcs6 also interacts genetically with Sep1. Thus, the Mcs6 complex, a direct activator of Cdc2, also influences the cell cycle transcriptional program, possibly through its TFIIH-associated kinase function. © 2005 by The American Society for Cell Biology. |
| Keywords: | controlled study; protein expression; protein phosphorylation; unclassified drug; mutation; nonhuman; protein function; cell cycle; cell division; gene expression; gene expression profiling; transcription factor; transcription, genetic; enzyme activation; oligonucleotide array sequence analysis; temperature; dna microarray; yeast; cyclin-dependent kinases; cyclin dependent kinase; rna polymerase ii; gene expression regulation, fungal; schizosaccharomyces; schizosaccharomyces pombe proteins; metazoa; schizosaccharomyces pombe; protein mcs6; transcription factor iih; genes, fungal; dna hybridization; protein pmh1; protein transcription factor sep1 |
| Journal Title: | Molecular Biology of the Cell |
| Volume: | 16 |
| Issue: | 6 |
| ISSN: | 1059-1524 |
| Publisher: | The American Society for Cell Biology |
| Date Published: | 2005-06-01 |
| Start Page: | 2734 |
| End Page: | 2745 |
| Language: | English |
| DOI: | 10.1091/mbc.E04-11-0982 |
| PUBMED: | 15829570 |
| PROVIDER: | scopus |
| PMCID: | PMC1142420 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 37" - "Export Date: 24 October 2012" - "CODEN: MBCEE" - "Source: Scopus" |
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